Exploring the binding mechanism of thioflavin-T to the β-amyloid peptide by blind docking method  

作　　者：ZHAO DeSheng CHEN YongXiang LIU Qian ZHAO YuFen LI YanMei 

机构地区：[1]Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education),Department of Chemistry,Tsinghua University,Beijing 100084,China

出　　处：《Science China Chemistry》2012年第1期112-117,共6页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China(20825206,20091350914 & 90913003);the Specialized Research Fund for the Doctoral Program of Higher Education (20100002110069)

摘　　要：Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand(ThT) and substrate(Aβ1-42) are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.Using blind dock method,we find that thioflavin-T（ThT） can bind to both monomers and fibrils of the full-length β-amyloid peptide（Aβ1-42） and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand（ThT） and substrate（Aβ1-42） are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.

关 键 词：THT AΒ1-42 AUTODOCK aggregation kinetic equation 

分 类 号：O629.7[理学—有机化学]